Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs

2008 ◽  
Vol 60 (11) ◽  
pp. 1507-1513
Author(s):  
William Crumb ◽  
Amine Benyamina ◽  
Christophe Arbus ◽  
George P. Thomas ◽  
Ricardo P. Garay ◽  
...  
2008 ◽  
Vol 60 (11) ◽  
pp. 1507-1513 ◽  
Author(s):  
William Crumb ◽  
Amine Benyamina ◽  
Christophe Arbus ◽  
George P. Thomas ◽  
Ricardo P. Garay ◽  
...  

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Guiscard Seebohm ◽  
Katja Steinke ◽  
Ulrike Henrion ◽  
Nicole Ettischer ◽  
Frank Sachse ◽  
...  

Infections with coxsackieviruses of type B (CVB) induce severe forms of acute and chronic myocarditis that are often accompanied by ventricular arrhythmias. The mechanisms underlying the development of virus-induced, life-threatening arrhythmia, remain largely elusive. Here, we show time-dependent CVB3-induced modulation of the cardiac ion channels Kv7.1, hERG1 and CaV1.2 in vitro. Channel protein localizations within cells and plasma membrane abundance are altered in infected mouse cardiac cells. In silico analyses of infected human myocytes suggest increased risk of arrhythmogenesis. These modifications are attenuated by the common Asian polymorphism KCNQ1-P448R, a genetic determinant preventing coxsackievirus-induced effects in vitro. This study provides a previously unknown explanation for the development of arrhythmias in enteroviral myocarditis, which will help to develop therapeutic strategies for arrhythmia treatment.


2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Sebastian Polak ◽  
Barbara Wiśniowska ◽  
Anna Glinka ◽  
Miłosz Polak

2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
P. Sager ◽  
B. Darpo ◽  
M.G. Midei ◽  
A.J. Camm ◽  
P. O'Grady ◽  
...  

2022 ◽  
Author(s):  
Camille Sanson ◽  
Rachid Boukaiba ◽  
Sylvie Houtmann ◽  
Magali-Anne Maizières ◽  
Sophie Fouconnier ◽  
...  

Abstract Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent flavonoids contained in citrus fruits, the flavanone naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. We hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP). To this end, we examined the effects of naringenin on the seven currents comprising the Comprehensive in vitro Pro-Arrhythmia (CiPA) panel for early arrhythmogenic risk assessment in drug discovery and development. We used automated patch-clamp of human ion channels heterologously expressed in mammalian cell lines to evaluate half-maximal inhibitory concentrations (IC50). Naringenin blocked all CiPA currents tested with IC50 values in the 30 µM – 100 µM concentration-range. The rank-order of channel sensitivity was the following: hERG > Kir2.1 > NaV1.5 late > NaV1.5 peak > KV7.1 > KV4.3 > CaV1.2. This multichannel inhibitory profile of naringenin suggests exercising caution when large amounts of grapefruit juice or other citrus juices enriched in this flavanone are drunk in conjunction with QT prolonging drugs or by carriers of congenital long QT syndromes.


2020 ◽  
Vol 886 ◽  
pp. 173542
Author(s):  
Marguerite Le Marois ◽  
Véronique Ballet ◽  
Camille Sanson ◽  
Magali-Anne Maizières ◽  
Thierry Carriot ◽  
...  

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1716
Author(s):  
Kun Tong ◽  
Ruotian Zhang ◽  
Fengzhi Ren ◽  
Tao Zhang ◽  
Junlin He ◽  
...  

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.


1965 ◽  
Vol 240 (7) ◽  
pp. 2845-2849
Author(s):  
Shlomo Burstein ◽  
Bhagu R. Bhavnani ◽  
Marcel Gut
Keyword(s):  

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